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World Journal of Urology May 2024Transperineal Prostate Biopsy (TPB) is a commonly used technique for the diagnosis of prostate cancer due to growing concerns related to infectious complications...
BACKGROUND
Transperineal Prostate Biopsy (TPB) is a commonly used technique for the diagnosis of prostate cancer due to growing concerns related to infectious complications associated with transrectal ultrasound-guided prostate biopsy (TRUSB). TPB is associated with an infective complication rate of near zero, however, acute urinary retention (AUR) remains the leading complication causing morbidity. Previously in TRUSB, there was weak evidence that alpha-blockers reduce AUR rates, and their usage has been extrapolated to clinical practice with TPB. This review aims to explore if there is an evidence base for using alpha-blockers to prevent AUR following TPB.
METHODS
A systematic approach was used to search Ovid Medline and Embase using keywords related to "Transperineal" and "Retention". Articles were then screened by applying inclusion and exclusion criteria to find studies that compared alpha-blocker recipients to no alpha-blocker use in the perioperative period and the subsequent effect on AUR in TPB.
RESULTS
361 records were identified in the initial search to produce 5 studies included in the final review. No randomised controlled trials (RCTs) were identified. One observational study showed a reduction in AUR rate from 12.5% to 5.3% with a single dose of tamsulosin. A previous systematic review of complications associated with prostate biopsy concluded there may be a potential benefit to alpha-blockers given in the TPB perioperative period. Three observational studies demonstrated a harmful effect related to alpha-blocker use; however, this was well explained by their clear limitations.
CONCLUSION
Based on this review and the extrapolation from TRUSB data, perioperative alpha-blockers may offer some weak benefits in preventing AUR following TPB. However, there is significant scope and need for an RCT to further develop the evidence base further given the significant gap in the literature and lack of a standard alpha blocker protocol in TPB.
Topics: Humans; Male; Urinary Retention; Prostate; Perineum; Prostatic Neoplasms; Adrenergic alpha-Antagonists; Postoperative Complications; Image-Guided Biopsy
PubMed: 38758413
DOI: 10.1007/s00345-024-05001-5 -
BMC Women's Health May 2024Overactive bladder (OAB) is a condition defined by urgency with or without incontinence which disproportionately affects female patients and has a negative impact on... (Review)
Review
BACKGROUND
Overactive bladder (OAB) is a condition defined by urgency with or without incontinence which disproportionately affects female patients and has a negative impact on sexual enjoyment and avoidance behaviour. Pharmacotherapy can be considered one of the main options for treating OAB. This research set out to determine the impact of pharmacotherapy on sexual function in females with OAB.
METHODS
This research used the robust methodology of a systematic review. The clinical question was formulated using the PICO (population, intervention, control, and outcomes) format to include females being treated with pharmacotherapy (anticholinergics or beta-3 adrenergic agonists) for idiopathic OAB with the use of a validated questionnaire assessing self-reported sexual function at baseline and post-treatment. The review incorporated the MEDLINE, PubMed and EMBASE databases. The AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) appraisal tool was used to guide the review process. Two reviewers worked independently in screening abstracts, deciding on the inclusion of full-texts, data extraction and risk of bias assessment.
RESULTS
In female patients with OAB, pharmacotherapy does seem to offer at least partial improvement in self-reported sexual function outcomes after 12 weeks of therapy. Still, the value of this finding is limited by an overall poor quality of evidence. Patients with a higher degree of bother at baseline stand to benefit the most from treatment when an improvement within this health-related quality of life domain is sought.
CONCLUSION
This research should form the basis for a well-conducted randomized controlled study to accurately assess sexual function improvements in females being treated with pharmacotherapy for OAB.
Topics: Humans; Urinary Bladder, Overactive; Female; Adrenergic beta-3 Receptor Agonists; Sexual Dysfunction, Physiological; Cholinergic Antagonists; Sexual Behavior; Quality of Life
PubMed: 38755593
DOI: 10.1186/s12905-024-03103-1 -
Journal of Clinical Hypertension... Jun 2024Despite substantial progress in understanding the complex pathophysiology, hypertension remains a serious public health challenge affecting over 1.2 billion adults aged...
Despite substantial progress in understanding the complex pathophysiology, hypertension remains a serious public health challenge affecting over 1.2 billion adults aged 30-79 years worldwide. Appropriate knowledge of the different pharmaceutical classes of antihypertensive agents and an understanding of the characteristics of individual molecules are essential to optimize clinical outcomes in patients with hypertension. We conducted a computer-assisted web interviewing (CAWI) quantitative survey in Italy, Poland, and Turkey to investigate physicians' prescriptions, knowledge, and perceptions of antihypertensive drugs with a focus on β-blockers, to assess antihypertensive usage patterns and the reasons underlying prescription choices. The survey findings show that β-blockers retain a pivotal role in the management of hypertension and are prescribed more often for patients with cardiovascular comorbidities than for patients with diabetic comorbidities. In all three countries, nebivolol is the only β-blocker among the ones analyzed which is consistently prescribed to 20% or more of patients and is overall the most prescribed one for the population with comorbid diabetes. In terms of specific β-blockers' features, this study revealed knowledge gaps that underline the need for educational activities focused on the differences among β-blockers, which are important in choosing the most suitable agent for individualized antihypertensive therapy.
Topics: Humans; Hypertension; Adrenergic beta-Antagonists; Turkey; Middle Aged; Poland; Italy; Male; Female; Adult; Practice Patterns, Physicians'; Antihypertensive Agents; Aged; Health Knowledge, Attitudes, Practice; Attitude of Health Personnel; Nebivolol; Surveys and Questionnaires; Physicians
PubMed: 38750668
DOI: 10.1111/jch.14819 -
Scientific Reports May 2024Despite the availability of various drugs for benign prostatic hyperplasia (BPH), alpha(α)-blockers are the preferred first-line treatment. However, there remains a... (Meta-Analysis)
Meta-Analysis Comparative Study
Despite the availability of various drugs for benign prostatic hyperplasia (BPH), alpha(α)-blockers are the preferred first-line treatment. However, there remains a scarcity of direct comparisons among various α-blockers. Therefore, this network meta-analysis (NMA) of randomized controlled trials (RCTs) aimed to evaluate the efficacy and safety of α-blockers in the management of BPH. A comprehensive electronic search covered PubMed, Embase, Ovid MEDLINE, and Cochrane Library until August 2023. The primary endpoints comprised international prostate symptom score (IPSS), maximum flow rate (Qmax), quality of life (QoL), and post-void residual volume (PVR), while treatment-emergent adverse events (TEAEs) were considered as secondary endpoints. This NMA synthesized evidence from 22 studies covering 3371 patients with six kinds of α-blockers with 12 dose categories. IPSS has been considerably improved by tamsulosin 0.4 mg, naftopidil 50 mg and silodosin 8 mg as compared to the placebo. Based on the p-score, tamsulosin 0.4 mg had the highest probability of ranking for IPSS, PVR, and Qmax, whereas doxazosin 8 mg had the highest probability of improving QoL. A total of 297 adverse events were reported among all the α-blockers, silodosin has reported a notable number of TEAEs. Current evidence supports α-blockers are effective in IPSS reduction and are considered safer. Larger sample size with long-term studies are needed to refine estimates of IPSS, QoL, PVR, and Qmax outcomes in α-blocker users.
Topics: Humans; Prostatic Hyperplasia; Male; Network Meta-Analysis; Adrenergic alpha-Antagonists; Treatment Outcome; Quality of Life; Randomized Controlled Trials as Topic; Tamsulosin
PubMed: 38750153
DOI: 10.1038/s41598-024-61977-5 -
Clinical and Translational Science May 2024Hypertensive patients with a higher proportion of genetic West African ancestry (%GWAA) have better blood pressure (BP) response to thiazide diuretics (TDs) and worse... (Randomized Controlled Trial)
Randomized Controlled Trial
Hypertensive patients with a higher proportion of genetic West African ancestry (%GWAA) have better blood pressure (BP) response to thiazide diuretics (TDs) and worse response to β-blockers (BBs) than those with lower %GWAA, associated with their lower plasma renin activity (PRA). TDs and BBs are suggested to reduce BP in the long term through vasodilation via incompletely understood mechanisms. This study aimed at identifying pathways underlying ancestral differences in PRA, which might reflect pathways underlying BP-lowering mechanisms of TDs and BBs. Among hypertensive participants enrolled in the Pharmacogenomics Evaluation of Antihypertensive Responses (PEAR) and PEAR-2 trials, we previously identified 8 metabolites associated with baseline PRA and 4 metabolic clusters (including 39 metabolites) that are different between those with GWAA <45% versus ≥45%. In the current study, using Ingenuity Pathway Analysis (IPA), we integrated these signals. Three overlapping metabolic signals within three significantly enriched pathways were identified as associated with both PRA and %GWAA: ceramide signaling, sphingosine 1- phosphate signaling, and endothelial nitric oxide synthase signaling. Literature indicates that the identified pathways are involved in the regulation of the Rho kinase cascade, production of the vasoactive agents nitric oxide, prostacyclin, thromboxane A2, and endothelin 1; the pathways proposed to underlie TD- and BB-induced vasodilatation. These findings may improve our understanding of the BP-lowering mechanisms of TDs and BBs. This might provide a possible step forward in personalizing antihypertensive therapy by identifying patients expected to have robust BP-lowering effects from these drugs.
Topics: Humans; Male; Female; Sodium Chloride Symporter Inhibitors; Hypertension; Blood Pressure; Middle Aged; Metabolomics; Adrenergic beta-Antagonists; Renin; Aged; Nitric Oxide Synthase Type III; Signal Transduction; Adult
PubMed: 38747311
DOI: 10.1111/cts.13816 -
Journal of Veterinary Cardiology : the... Jun 2024A nine-year-old spayed female domestic shorthair cat with a previous diagnosis of hypertrophic cardiomyopathy and treated for one month with atenolol (6.25 mg q 12 h)...
A nine-year-old spayed female domestic shorthair cat with a previous diagnosis of hypertrophic cardiomyopathy and treated for one month with atenolol (6.25 mg q 12 h) was referred for respiratory distress and anorexia. The cat was diagnosed with pulmonary oedema secondary to obstructive hypertrophic cardiomyopathy. After stabilisation, she was discharged with furosemide (1 mg/kg q 12 h), clopidogrel (18.75 mg q 24 h), atenolol (6.25 mg q 12 h), and mirtazapine (2 mg/cat q 24 h) to increase appetite. At recheck, the cat was lethargic and presented with severe bradycardia with a junctional escape rhythm and ventriculoatrial conduction. The mirtazapine was discontinued due to its possible side-effects on cardiac rhythm. After three days, the atenolol was halved because the bradyarrhythmia was still present. After 10 days, the rhythm returned to sinus; atenolol was reintroduced twice daily with no further side-effects. The absence of a sinus rhythm with a junctional escape rhythm and P' retroconduction is compatible with a third-degree sinus block or a sinus standstill; the differentiation of these rhythm disturbances is impossible, based on the surface electrocardiogram (ECG). The sinus rhythm was restored after mirtazapine was withdrawn. However, it is not possible to rule out the role of the atenolol or the combined effect of the two drugs. The cat was affected by hypertrophic cardiomyopathy, and the role of myocardial remodelling cannot be excluded. This is the first time that a bradyarrhythmia consequent to the treatment with atenolol and mirtazapine was described in a cat.
Topics: Female; Mirtazapine; Animals; Atenolol; Cats; Cat Diseases; Cardiomyopathy, Hypertrophic; Bradycardia; Mianserin; Adrenergic beta-1 Receptor Antagonists
PubMed: 38735230
DOI: 10.1016/j.jvc.2024.03.003 -
Journal of Anxiety Disorders Jun 2024Exposure therapy is an evidence-based treatment option for anxiety-related disorders. Many patients also take medication that could, in principle, affect exposure... (Meta-Analysis)
Meta-Analysis
Exposure therapy is an evidence-based treatment option for anxiety-related disorders. Many patients also take medication that could, in principle, affect exposure therapy efficacy. Clinical and laboratory evidence indeed suggests that benzodiazepines may have detrimental effects. Large clinical trials with propranolol, a common beta-blocker, are currently lacking, but several preclinical studies do indicate impaired establishment of safety memories. Here, we investigated the effects of propranolol given prior to extinction training in 9 rat studies (N = 215) and one human study (N = 72). A Bayesian meta-analysis of our rat studies provided strong evidence against propranolol-induced extinction memory impairment during a drug-free test, and the human study found no significant difference with placebo. Two of the rat studies actually suggested a small beneficial effect of propranolol. Lastly, two rat studies with a benzodiazepine (midazolam) group provided some evidence for a harmful effect on extinction memory, i.e., impaired extinction retention. In conclusion, our midazolam findings are in line with prior literature (i.e., an extinction retention impairment), but this is not the case for the 10 studies with propranolol. Our data thus support caution regarding the use of benzodiazepines during exposure therapy, but argue against a harmful effect of propranolol on extinction learning.
Topics: Propranolol; Animals; Fear; Extinction, Psychological; Rats; Humans; Adrenergic beta-Antagonists; Male; Memory; Midazolam; Adult; Bayes Theorem; Female; Conditioning, Classical; Young Adult
PubMed: 38733644
DOI: 10.1016/j.janxdis.2024.102870 -
International Journal of Molecular... Apr 2024In contrast to cats and dogs, here we report that the α-adrenergic receptor antagonist yohimbine is emetic and corresponding agonists clonidine and dexmedetomidine... (Comparative Study)
Comparative Study
A Comparative Study of the Antiemetic Effects of α-Adrenergic Receptor Agonists Clonidine and Dexmedetomidine against Diverse Emetogens in the Least Shrew () Model of Emesis.
In contrast to cats and dogs, here we report that the α-adrenergic receptor antagonist yohimbine is emetic and corresponding agonists clonidine and dexmedetomidine behave as antiemetics in the least shrew model of vomiting. Yohimbine (0, 0.5, 0.75, 1, 1.5, 2, and 3 mg/kg, i.p.) caused vomiting in shrews in a bell-shaped and dose-dependent manner, with a maximum frequency (0.85 ± 0.22) at 1 mg/kg, which was accompanied by a key central contribution as indicated by increased expression of c-, serotonin and substance P release in the shrew brainstem emetic nuclei. Our comparative study in shrews demonstrates that clonidine (0, 0.1, 1, 5, and 10 mg/kg, i.p.) and dexmedetomidine (0, 0.01, 0.05, and 0.1 mg/kg, i.p.) not only suppress yohimbine (1 mg/kg, i.p.)-evoked vomiting in a dose-dependent manner, but also display broad-spectrum antiemetic effects against diverse well-known emetogens, including 2-Methyl-5-HT, GR73632, McN-A-343, quinpirole, FPL64176, SR141716A, thapsigargin, rolipram, and ZD7288. The antiemetic inhibitory ID values of dexmedetomidine against the evoked emetogens are much lower than those of clonidine. At its antiemetic doses, clonidine decreased shrews' locomotor activity parameters (distance moved and rearing), whereas dexmedetomidine did not do so. The results suggest that dexmedetomidine represents a better candidate for antiemetic potential with advantages over clonidine.
Topics: Animals; Male; Adrenergic alpha-2 Receptor Agonists; Adrenergic alpha-2 Receptor Antagonists; Antiemetics; Clonidine; Dexmedetomidine; Disease Models, Animal; Emetics; Shrews; Vomiting; Yohimbine
PubMed: 38731821
DOI: 10.3390/ijms25094603 -
European Journal of Epidemiology Apr 2024Prospective benchmarking of an observational analysis against a randomized trial increases confidence in the benchmarking process as it relies exclusively on aligning...
Prospective benchmarking of an observational analysis against a randomized trial increases confidence in the benchmarking process as it relies exclusively on aligning the protocol of the trial and the observational analysis, while the trials findings are unavailable. The Randomized Evaluation of Decreased Usage of Betablockers After Myocardial Infarction (REDUCE-AMI, ClinicalTrials.gov ID: NCT03278509) trial started recruitment in September 2017 and results are expected in 2024. REDUCE-AMI aimed to estimate the effect of long-term use of beta blockers on the risk of death and myocardial following a myocardial infarction with preserved left ventricular systolic ejection fraction. We specified the protocol of a target trial as similar as possible to that of REDUCE-AMI, then emulated the target trial using observational data from Swedish healthcare registries. Had everyone followed the treatment strategy as specified in the target trial protocol, the observational analysis estimated a reduction in the 5-year risk of death or myocardial infarction of 0.8 percentage points for beta blockers compared with no beta blockers; effects ranging from an absolute reduction of 4.5 percentage points to an increase of 2.8 percentage points in the risk of death or myocardial infarction were compatible with our data under conventional statistical criteria. Once results of REDUCE-AMI are published, we will compare the results of our observational analysis against those from the trial. If this prospective benchmarking is successful, it supports the credibility of additional analyses using these observational data, which can rapidly deliver answers to questions that could not be answered by the initial trial. If benchmarking proves unsuccessful, we will conduct a "postmortem" analysis to identify the reasons for the discrepancy. Prospective benchmarking shifts the investigator focus away from an endeavour to use observational data to obtain similar results as a completed randomized trial, to a systematic attempt to align the design and analysis of the trial and the observational analysis.
Topics: Humans; Benchmarking; Myocardial Infarction; Sweden; Registries; Prospective Studies; Adrenergic beta-Antagonists; Female; Male; Aged; Randomized Controlled Trials as Topic; Middle Aged
PubMed: 38717556
DOI: 10.1007/s10654-024-01119-3 -
Psychopharmacology Jul 2024Medications are urgently needed to treat symptoms of drug withdrawal and mitigate dysphoria and psychiatric comorbidities that drive opioid abuse and relapse. ITI-333 is...
RATIONALE
Medications are urgently needed to treat symptoms of drug withdrawal and mitigate dysphoria and psychiatric comorbidities that drive opioid abuse and relapse. ITI-333 is a novel molecule in development for treatment of substance use disorders, psychiatric comorbidities, and pain.
OBJECTIVE
Characterize the preclinical profile of ITI-333 using pharmacological, behavioral, and physiological assays.
METHODS
Cell-based assays were used to measure receptor binding and intrinsic efficacy of ITI-333; animal models were employed to assess effects on opioid reinstatement, precipitated oxycodone withdrawal, and drug abuse liability.
RESULTS
In vitro, ITI-333 is a potent 5-HT receptor antagonist (K = 8 nM) and a biased, partial agonist at μ-opioid (MOP) receptors (K = 11 nM; lacking β-arrestin agonism) with lesser antagonist activity at adrenergic α (K = 28 nM) and dopamine D (K = 50 nM) receptors. In vivo, ITI-333 blocks 5-HT receptor-mediated head twitch and MOP receptor-mediated effects on motor hyperactivity in mice. ITI-333 alone is a naloxone-sensitive analgesic (mice) which suppresses somatic signs of naloxone-precipitated oxycodone withdrawal (mice) and heroin cue-induced reinstatement responding without apparent tolerance or physical dependence after chronic dosing (rats). ITI-333 did not acutely impair gastrointestinal or pulmonary function (rats) and was not intravenously self-administered by heroin-maintained rats or rhesus monkeys.
CONCLUSIONS
ITI-333 acts as a potent 5-HT receptor antagonist, as well a biased MOP receptor partial agonist with low intrinsic efficacy. ITI-333 mitigates opioid withdrawal/reinstatement, supporting its potential utility as a treatment for OUD.
Topics: Animals; Mice; Male; Substance Withdrawal Syndrome; Rats; Humans; Rats, Sprague-Dawley; Receptors, Opioid, mu; Serotonin 5-HT2 Receptor Antagonists; Substance-Related Disorders; Opioid-Related Disorders; Dose-Response Relationship, Drug; Oxycodone; Analgesics, Opioid; Self Administration; Cricetulus; CHO Cells
PubMed: 38710856
DOI: 10.1007/s00213-024-06578-w